Who is who within the universe of TREM-like transcripts (TREML)?

The Triggering Receptor Expressed on Myeloid Cells (TREM) family of receptors plays a crucial role in the immune response across various species. Particularly, TREM-1 and TREM-2 have been extensively studied, both in terms of their applications and their expression sites and signaling pathways. However, the same is not observed for the other family members collectively known as TREM-like-transcripts (TREML). The TREML family consists of eight receptors, with TREML1-5 identified in humans and mice, TREML-6 exclusive found in mice, TREML-7 in dogs and horses, and TREML-8 in rabbits and opossums. Despite the limited data available on the TREML members, they have been implicated in different immune and non-immune activities, which have been proposed to display both pro and anti-inflammatory activities, and to influence fundamental biological processes such as coagulation, bone and neurological development. In this review, we have compiled available information regarding the already discovered members of the family and provided foundational framework for understanding the function, localization, and therapeutic potential of all TREML members. Additionally, we hope that this review may shed light on this family of receptors, whose underlying mechanisms are still awaiting elucidation, while emphasizing the need for future studies to explore their functions and potential therapeutic application.

The CDR3 region as the major driver of TREM-1 interaction with its ligands, an in silico characterization.

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor heavily investigated in infectious and non-infectious diseases. Because of its role in amplifying inflammation, TREM-1 has been explored as a diagnostic/prognostic biomarker. Further, as the receptor has been implicated in the pathophysiology of several diseases, therapies aiming at modulating its activity represent a promising strategy to constrain uncontrolled inflammatory or infectious diseases. Despite this, several aspects concerning its interaction with ligands and activation process, remain unclear. Although many molecules have been suggested as TREM-1 ligands, only five have been confirmed to interact with the receptor: actin, eCIRP, HMGB1, Hsp70 and PGLYRP1. However, the domains involved in the interaction between the receptor and these proteins are not clarified yet. Therefore, here we used in silico approaches to investigate the putative binding domains in the receptor, using hot spots analysis, molecular docking and molecular dynamics simulations between TREM-1 and its five known ligands. Our results indicated the complementarity-determining regions (CDRs) of the receptor as the main mediators of antigen recognition, especially the CDR3 loop. We believe that our study could be used as structural basis for the elucidation of TREM-1's recognition process, and may be useful for prospective in silico and biological investigations exploring the receptor in different contexts.

Immunoinformatics-guided design of a multi-valent vaccine against Rotavirus and Norovirus (ChRNV22).

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far. Therefore, we used immunoinformatics tools to develop a multi-epitope vaccine (ChRNV22) to prevent severe AG by RV and NV. Epitopes were predicted against 17 prevalent genotypes of four structural proteins (NV's VP1, RV's VP4, VP6 and VP7), and then assembled in a chimeric protein, with two small adjuvant sequences (tetanus toxin P2 epitope and a conserved sequence of RV's enterotoxin, NSP4). Simulations of the immune response and interactions with immune receptors indicated the immunogenic properties of ChRNV22, including a Th1-biased response. In silico search for putative host-homologous, allergenic and toxic regions also indicated the vaccine safety. In summary, we developed a multi-epitope vaccine against different NV and RV genotypes that seems promising for the prevention of severe AG, which will be further assessed by in vivo tests.

The role of the triggering receptor expressed on myeloid cells-1 (TREM-1) in non-bacterial infections.

The triggering receptor expressed on myeloid cells 1 (TREM-1) is a receptor of the innate immune system, expressed mostly by myeloid cells and primarily associated with pro- inflammatory responses. Although the exact nature of its ligands has not yet been fully elucidated, many microorganisms or danger signals have been proposed as inducers of its activation or the secretion of sTREM-1, the soluble form with putative anti-inflammatory effects. In the course of the 20 years since its first description, several studies have investigated the involvement of TREM-1 in bacterial infections. However, the number of studies describing the role of TREM-1 in fungal, viral and parasite-associated infections has only increased in the last few years, showing a diverse contribution of the receptor in these scenarios, with beneficial or detrimental activities depending on the context. Therefore, this review aims to discuss how TREM-1 may influence viral, fungal and parasitic infection outcomes, highlighting its potential as a therapeutic target and biomarker for diagnosis and prognosis of non-bacterial infectious diseases.

Is it possible to track intracellular chitosan nanoparticles using magnetic nanoparticles as contrast agent?

Drug delivery systems prepared with nanostructures are able to overcome biological barriers. However, one of the main challenges in the use of these nanosystems is their internalization by macrophages. This study aims to prepare and characterize chitosan nanoparticles incorporating maghemite nanoparticles and investigate their intracellular tracking in RAW 264.7 macrophages in vitro. Then, maghemite nanoparticles were encapsulated within chitosan nanoparticles by ionotropic gelification method. The images from transmission electron microscopy were used to investigate the intracellular penetration of conjugated nanoparticles by macrophages using different times. Our data suggests that magnetic nanoparticles are suitable to act as a contrast agent to investigate the cellular internalization of chitosan nanoparticles.